1. Field of the Invention
The present invention relates to the glycoconjugates, the sialic acid (α-(2→6))-D-aminopyranose derivatives, their conjugates to proteins or polypeptides and the synthesis methods thereof are of particular interest. And the present invention also relates to the application of these compounds in the preparation of anti-tumor drugs. The present invention falls within the area of anti-tumor vaccines.
2. Description of the Background Art
In recent years, vaccines based on the tumor-associated carbohydrate antigens (TACAs) are regarded as one of the research hotspots. STn antigen, a sialic acid-containing disaccharide, is expressed abundantly on breast, prostate, pancreas, colorectal, lung, gastric, and ovarian cancers; but only expressed limitedly on normal cells, which makes STn may serve as a important target in tumor immunotherapy. Based on this, Theratope® (acquired by Merck KGaA), a STn-KLH (keyhole limpet hemocyanin) conjugate, was developed at Biomira Inc., Canada to prevent metastasis of breast and rectal cancers. However, Theratope® was found not to improve time to progression (TTP) or overall survival (OS) when subjected to phase III clinical trial. Improved TTP was achieved only when patients were treated in conjugation with hormone therapy, leading to the prolonged time by 2.5 months (previously 5-8 months) of administration of hormone alone. The dependence on hormone of its anti-tumor activity eclipsed the efficacy of Theratope®. The major obstacle of carbohydrate-based anti-tumor vaccines, as was encountered by Theratope®, is their unsatisfactory performance in inducing immune responses. The conjugation of carbohydrate antigens to immunogenic carrier proteins was generally adopted, but was proved partially by Theratope® relatively ineffective for tumor-associated antigens.